Topical tacrolimus in atopic dermatitis: Effects of ... - Helda - Helsinki.fi

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ABBREVIATIONS AD Atopic dermatitis BHR Bronchial hyper-responsiveness BSA Body surface area CLA Cutaneous lymphocyte-associated antigen Fc�RI/ Fc�RII High-affinity receptor for IgE type I/II FK506 Tacrolimus molecule HSV Herpes Simplex virus IDEC Inflammatory dendritic epidermal cell IFN Interferon IgE, S-IgE Immunoglobulin E, Serum immunoglobulin E IL Interleukin LC Langerhans cell MMP Matrix metalloproteinase NF-AT Nuclear factor for activated T cells PEF Peak expiratory flow PICP Carboxyterminal propeptide of type I collagen PINP / PIIINP Aminoterminal propeptide of type I / III collagen S. aureus Staphylococcus aureus SBF Suction blister fluid SPT Skin prick tests TEWL Transepidermal water loss TIMP Tissue inhibitor of metalloproteinase TGF-� Transforming growth factor � Th1 / Th2 T helper cells type 1 / type 2 UV Ultraviolet VAS Visual analogue scale 8
ABSTRACT Objective: Patients with atopic dermatitis often have a poor long-term response to conventional topical or systemic treatments. They suffer from staphylococcal superinfections, skin atrophy due to corticosteroid use, and may have asthma and allergic rhinitis. The association between atopic skin and airways has been thought to result from epicutaneous sensitization through the inflamed skin, which leads to systemic T cell responses and airway hyperreactivity. Only a few, usually short-term, studies have addressed the effects of different treatments of atopic dermatitis on these problems. Tacrolimus ointment is the first topical compound suitable for long-term treatment. The aim of this thesis was to evaluate the effects of long-term topical tacrolimus treatment on cutaneous staphylococcal colonization, collagen synthesis, and symptoms and signs of asthma and allergic rhinitis. Methods: Patients with moderate-to-severe atopic dermatitis were treated with intermittent 0.1% tacrolimus ointment in prospective, open, long-term studies lasting for 6 to 48 months. In Study I, staphylococcal colonization of their skin was followed by bacterial cultures for 6 to 12 months. In Study II, skin thickness and collagen synthesis were followed by skin ultrasound and procollagen I and III propeptide concentrations of the suction blister fluid samples for 12 to 24 months and compared with a group of atopic dermatitis patients treated with topical corticosteroids and with a group of healthy subjects. Study III was a cross-sectional study including atopic dermatitis patients and healthy controls. The occurrence of respiratory symptoms was determined with a questionnaire, bronchial hyper-responsiveness by bronchial histamine challenge, and sputum eosinophilia by induced sputum test. Atopy status was assessed by skin prick test reactivity and serum immunoglobulin E concentration. In Study V, the same parameters as in Study III were assessed in atopic dermatitis patients before and after 12 to 48 months of topical tacrolimus treatment. Study IV was a retrospective follow-up of the effect of tacrolimus 0.03% ointment on severe atopic blepharoconjunctivitis and conjunctival cytology samples. Results: The clinical response of atopic dermatitis to topical tacrolimus was very good in all studies (p�0.008). Staphylococcal colonization decreased significantly, and the effect was sustained throughout the study period (p=0.01). Skin thickness (p
Page 1 and 2: Topical tacrolimus in atopic dermat
Page 3: To Juha and Veera
Page 6 and 7: Effects of treatment on skin barrie
Page 10 and 11: and bronchial hyper-responsiveness
Page 12 and 13: REVIEW OF THE LITERATURE Atopic der
Page 14 and 15: probably plays a protective role ag
Page 16 and 17: e induced by IL-2 and bacterial sup
Page 18 and 19: and has a lower risk for asthma and
Page 20 and 21: Both asthma and allergic rhinitis i
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Page 24 and 25: naturally occurring glucocorticoste
Page 26 and 27: severe atopic dermatitis, hand ecze
Page 28 and 29: and their complex inhibits activati
Page 30 and 31: extent of topical absorption decrea
Page 32 and 33: of one type of treatment can be bet
Page 34 and 35: liver (Burgeson & Nimni 1992). At l
Page 36 and 37: UVA therapy suppresses collagen syn
Page 38 and 39: AIMS OF THE STUDY Atopic dermatitis
Page 40 and 41: Inclusion criteria Patients with mo
Page 42 and 43: Methods Treatment with tacrolimus o
Page 44 and 45: Respiratory symptoms and findings T
Page 46 and 47: Statistical methods In Studies I, I
Page 48 and 49: Staphylococcus aureus colonization
Page 50 and 51: Table 7. Subject characteristics; o
Page 52 and 53: physician-diagnosed asthma (2.09 vs
Page 54 and 55: In Study V, eight (12%) patients us
Page 56 and 57: Skin collagen synthesis The results
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Results of the present uncontrolled
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al. 1986, Burrows et al. 1989, Kono
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ACKNOWLEDGEMENTS This study was car
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REFERENCES Aberer W, Wolff K. Syste
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Bousquet J; Jeffery PK, Busse WW, J
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Dold S, Wjst M, von Mutius E, Reitm
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Haapasaari K. Rossi O. Risteli J. O
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Krutmann JT, Morita A. Phototherapy
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Nishino K, Fukushima A, Okamoto S,
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Quanjer PH, Tammeling GJ, Cotes JE,
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Schultz-Larsen F, Diepgen T, Svenso
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Tsai WC, Pang JH, Hsu CC, Chu NK, L
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ERRATA Page 36: In Table 2 in the c
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